Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

Chlorin e6-modified iron oxide nanoparticles for photothermal-photodynamic ablation of glioblastoma cells.

Introduction: The effective treatment of glioblastoma still remains a great challenge. We herein report the development of chlorin e6 (Ce6)-conjugated iron oxide (Fe3O4-Ce6) nanoparticles for ablation of glioblastoma cells via combining photothermal therapy (PTT) with photodynamic therapy (PDT). Methods: Ce6 was conjugated to the synthesized Fe3O4 nanoparticles to form Fe3O4-Ce6 nanoparticles displaying the optical property of Ce6. Results and discussion: Under 808 nm laser irradiation, Fe3O4-Ce6 nanoparticles generated heat and the temperature increase did not have obvious changes after five cycles of laser irradiation, suggesting their good photothermal effect and photothermal stability. In addition, 660 nm laser irradiation of Fe3O4-Ce6 nanoparticles produced singlet oxygen (1O2) to mediate PDT. The Fe3O4-Ce6 nanoparticles without laser irradiation showed a low cytotoxicity, but they would obviously kill C6 cancer cells after laser irradiation via the combinational effect of PTT and PDT. Fe3O4-Ce6 nanoparticles thus could be used as a nanotherapeutic agent for combinational ablation of glioblastoma cells.

Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study.

PURPOSE: ASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) in the real-world setting. Here we report the results of Chinese patients in ASTRIS study. METHODS: Adults with EGFR T790M-positive advanced NSCLC pretreated with EGFR-tyrosine kinase inhibitor (EGFR-TKI), having a WHO performance status score of 0-2 and asymptomatic, stable central nervous system (CNS) metastases were included. All patients received once-daily osimertinib 80 mg orally. The outcomes included investigator-assessed clinical response, progression-free survival (PFS), time-to-treatment discontinuation (TTD), and safety. RESULTS: A total of 1350 patients were included. Response rate was 55.7% (95% confidence interval [CI] 0.53-0.58). The median PFS and the median TTD were 11.7 months (95% CI 11.1-12.5) and 13.9 months (95% CI 13.1-15.2), respectively. Overall, 389 patients (28.8%) had at least one protocol-specified adverse event (AE); AEs of interstitial lung diseases/pneumonitis-like events and QT prolongation were reported in 3 (0.2%) and 59 (4.4%) patients, respectively. CONCLUSION: Osimertinib was effective in Chinese patients with T790M-positive NSCLC who had progressed after first- or second-generation EGFR-TKI in real-word setting and the results were consistent with ASTRIS study overall population and AURA studies. No new safety signals or events were identified. CLINICAL TRIAL NUMBER: NCT02474355.

Impact of a novel prognostic model on allogeneic hematopoietic stem cell transplantation outcomes in patients with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curable treatment. The outcomes after transplant are influenced by both disease characteristics and patient comorbidities. To develop a novel prognostic model to predict the post-transplant survival of CMML patients, we identified risk factors by applying univariable and multivariable Cox proportional hazards regression to a derivation cohort. In multivariable analysis, advanced age (hazard ratio [HR] 3.583), leukocyte count (HR 3.499), anemia (HR 3.439), bone marrow blast cell count (HR 2.095), and no chronic graft versus host disease (cGVHD; HR 4.799) were independently associated with worse survival. A novel prognostic model termed ABLAG (Age, Blast, Leukocyte, Anemia, cGVHD) was developed and the points were assigned according to the regression equation. The patients were categorized into low risk (0-1), intermediate risk (2, 3), and high risk (4-6) three groups and the 3-year overall survival (OS) were 93.3% (95%CI, 61%-99%), 78.9% (95%CI, 60%-90%), and 51.6% (95%CI, 32%-68%; p < .001), respectively. In internal and external validation cohort, the area under the receiver operating characteristic (ROC) curves of the ABLAG model were 0.829 (95% CI, 0.776-0.902) and 0.749 (95% CI, 0.684-0.854). Compared with existing models designed for the nontransplant setting, calibration plots, and decision curve analysis showed that the ABLAG model revealed a high consistency between predicted and observed outcomes and patients could benefit from this model. In conclusion, combining disease and patient characteristic, the ABLAG model provides better survival stratification for CMML patients receiving allo-HSCT.

Tislelizumab-related enteritis successfully treated with adalimumab: A case report.

BACKGROUND: With programmed death-1 (PD-1) inhibitors becoming the standard treatment for lung cancer, PD-1-related adverse reactions and treatment have gradually become prominent. CASE SUMMARY: First reported case of tislelizumab-related enteritis successfully treated with adalimumab 40mg every 2 wk for 3 times in an advanced lung cancer patient who received first-line tislelizumab/pemetrexed/carboplatin for 4 cycles. The patient continued receiving the treatment of pemetrexed/carboplatin after symptoms, abdominal computed tomography and colonoscopy improved, significant diarrhea was not occurred. CONCLUSION: Adalimumab can be an effective treatment option for patients with PD-1 antibody related enteritis if they do not respond well to glucocorticoid treatment.

A Combination of Serum Biomarkers in Elderly Patients with Sarcopenia: A Cross-Sectional Observational Study.

BACKGROUND: The pathogenesis of sarcopenia in the elderly has not yet been fully understood. This study aimed to explore the relationship between sarcopenia and several serum biomarkers in elderly population. METHODS: It was an observational cross-sectional study of data collected from 70 patients. According to the criteria of the Asian Working Group for Sarcopenia (AWGS), subjects were divided into the sarcopenia group and nonsarcopenic group. We compared age, body mass index (BMI), biochemical indexes, smoking status, underlying disease, muscle mass, handgrip strength (HS), gait speed (GS), skinfold thickness, muscle thickness, and IL-6, IL-10, IL-17A, and TNF-α levels between these groups. RESULTS: Of the 70 subjects, 35 patients were diagnosed with sarcopenia. The number of men was higher than that of women in both groups. The patients with sarcopenia were older and had lower BMI and muscle thickness but higher SARC-F questionnaire scores. However, the difference in smoking status and skinfold thickness between these two groups were not statistically significant. Higher IL-6, IL-17A, and TNF-α levels were observed in participants with sarcopenia (P < 0.05). Patients with sarcopenia had a lower IL-10 level. Positive associations were present between the severity of sarcopenia and IL-6, IL-17A, and TNF-α levels, while there was an inverse correlation between the presence of sarcopenia and IL-10 level. CONCLUSIONS: Our research found that in sarcopenic elderly subjects, the serum levels of several biomarkers, such as IL-6, IL-17A, and TNF-α, were higher than those in nonsarcopenic elderly persons. Further studies are needed to explore the possible molecular mechanisms and discover new therapeutic targets.

Three-year follow-up and patient-reported outcomes from CheckMate 078: Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer.

OBJECTIVES: In the phase 3 CheckMate 078 study, nivolumab prolonged overall survival (OS) and showed a favorable safety profile versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer (aNSCLC). However, long-term efficacy, safety, and health-related quality of life findings with second-line nivolumab are very limited in Asian patients with previously treated aNSCLC. Here, we report updated clinical data and patient-reported outcomes (PROs) from the phase 3 CheckMate 078 trial with a 3-year minimum follow-up. MATERIALS AND METHODS: Patients with aNSCLC and disease progression after platinum-doublet chemotherapy were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m2 every 3 weeks) until progression or unacceptable toxicity. The primary endpoint was OS; secondary endpoints included objective response rate, progression-free survival, safety, and disease-related symptom deterioration assessed using the Lung Cancer Symptom Scale (LCSS) by Week 12. Additional PRO assessments were exploratory endpoints. RESULTS: At ≥ 37.3 months follow-up, 3-year OS rates were 19% with nivolumab and 12% with docetaxel; 30% and 0% of responders remained in response for ≥ 3 years, respectively. Incidence of treatment-related adverse events occurring after 2 years was lower than during the first 2 years. No new treatment-related deaths were reported. By Week 12 of treatment, rates of disease-related symptom deterioration were 32% with nivolumab and 47% with docetaxel. Completion rates for PRO questionnaires were ≥ 80% in both arms. Clinically meaningful and sustained improvements in LCSS Average Symptom Burden Index scores and delayed time to first symptom deterioration were observed with nivolumab against docetaxel. CONCLUSIONS: At 3 years, nivolumab continued to demonstrate survival benefit versus docetaxel, exhibiting improvements in disease-related symptoms and overall health status in a predominantly Chinese patient population with previously treated aNSCLC. No new safety signals were observed. These findings are similar to the global population.

Adherence to the Dietary Approaches to Stop Hypertension diet reduces the risk of breast cancer: A systematic review and meta-analysis.

Background: Despite increasing evidence for the association of adherence to the Dietary approaches to stop hypertension (DASH) diet with breast cancer risk, the results remain inconclusive. The purpose of the current systematic review was to summarize the evidence from previous observational studies and explore the potential association between DASH diet and breast cancer risk using meta-analysis. Methods: A comprehensive literature search was conducted using the databases of PubMed, Web of Science, CNKI and Wanfang Data to identify the relevant publications from inception up to July 2022. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest categories of DASH score in relation to breast cancer risk, using a random-effects model. The Cochran's Q test and I-squared (I 2) statistic were used to detect the sources of heterogeneity among the included studies. Results: Overall, eleven studies, involving 23,254 breast cancer cases and 449,273 participants, were included in this systematic review and meta-analysis. Combining 16 effect sizes from 11 studies, a significant inverse association between adherence to the DASH diet and risk of breast cancer was observed (RR = 0.79; 95% CI: 0.70, 0.90, P < 0.0001). Stratified analysis showed a significant association between adherence to the DASH diet and risk of breast cancer in case-control studies (RR = 0.49; 95% CI: 0.27-0.89, P = 0.019), and a marginally significant association in prospective cohort studies (RR = 0.92; 95% CI: 0.86-0.98, P = 0.014), respectively. Besides, a more significant association between DASH score and reduced risk of breast cancer was observed in Asian countries (RR = 0.50; 95% CI: 0.31-0.81, P = 0.005) than in the United States (RR = 0.93; 95% CI: 0.89-0.99, P = 0.012). Similarly, when we conducted analyses separately by menopausal status, we found a significant inverse association between DASH diet and breast cancer risk in postmenopausal women (RR = 0.58; 95% CI: 0.39-0.87, P = 0.008). Conclusion: The results of this systematic review and meta-analysis indicate a significant inverse association between adherence to the DASH diet and risk of breast cancer. Further large prospective studies and randomized controlled trials are required to confirm our findings.

Diagnosis and treatment of primary pulmonary enteric adenocarcinoma: Report of Six cases.

BACKGROUND: Primary pulmonary enteric adenocarcinoma (PEAC) is a very rare subtype of invasive adenocarcinoma, and there have been no large studies on PEAC to date. Therefore, it is necessary to obtain much more information about the clinical and pathological features, diagnosis, differential diagnosis, and treatment of PEAC. CASE SUMMARY: All clinical data of six patients with confirmed PEAC from 2013 to 2018 were collected, and data on diagnosis, differential diagnosis, and treatment of PEAC are discussed combined with all the associated literature. The mean age of six patients was 64.0 ± 5.6 (59-73) years old. Their clinical manifestations were heterogeneous, and during their disease course, there were no gastrointestinal symptoms. There was no evidence from colonoscopy or imaging studies to suggest digestive tract tumors or new metastases. The most commonly mutated gene was KRAS (50.0%), and the pathological features of the six cases were similar to those of colorectal cancer. CDX2 (83.3%) and CK7 (66.7%) had the highest positive rates upon immunohistochemical examination. In the associated literature, 252 cases were identified, and the most commonly mutated gene was KRAS (42.9%). Additionally, CDX2 (68.3%) and CK7 (85.8%) had the highest positive rates. Patients mainly received surgery, chemotherapy, and radiotherapy, immunotherapy was not included. CONCLUSION: Positive results for CDX2 and CK7 play an important role in the diagnosis and differential diagnosis of PEAC, and immunotherapy or targeted therapy focused on KRAS needs to be further studied for the treatment of PEAC.

The Chinese Thoracic Oncology Group (CTONG) therapeutic option scoring system: a multiple-parameter framework to assess the value of lung cancer treatment options.

BACKGROUND: Currently, there is no standard context that conforms to the Chinese national framework for evaluating medical decisions regarding the treatment of lung cancer. METHODS: This draft was formulated after a systematic review and a focus group discussion among 20 experts, who were senior physicians with extensive clinical experience from the Chinese Thoracic Oncology Group (CTONG) task force. Subsequently, a draft and a five-point Likert scale were sent to 300 CTONG working group members. These were modified according to feedback from a four-round modified Delphi approach. Hence, the first version of the 'Therapeutic option of lung cancer: CTONG scoring system' was formulated. Afterward, a corresponding questionnaire was designed to collect opinions on the weight allocation of various indicators. This was issued through the WeChat platform, "Oncology News" application and e-mails from October 23, 2020, to November 25, 2020. Participants from numerous occupations in cancer-related fields from various regions of China were included in the study. Overall and subgroup analyses regarding weight allocations were performed. The differences between participant-allocated and reference weights were considered to adjust the framework. RESULTS: The framework contained four aspects and six indicators, including efficacy [progression-free survival (PFS)/overall survival (OS) and subsequent treatment], safety [treatment-related severe adverse event (SAE), dose adjustment], quality of life (Qol), and compensation. The reference weights were 50%, 5%, 10%, 5%, 10%, and 20% for each indicator. By November 25, 2020, 1,043 valid questionnaires had been obtained. The majority of the questionnaires were completed by physicians (86.5%). Subgroup analysis among the various groups showed an overall consistent trend. Besides, significant differences between the participant-allocated and reference weights were found among PFS/OS (difference: -11.5%), compensation (difference: -10.1%), and subsequent treatment (difference: 9.7%) indicators. After discussion, the final weight allocations were set at 45%, 10%, 15%, 5%, 10%, and 15% for PFS/OS, subsequent treatment, treatment-related SAE, dose adjustment, Qol, and compensation, respectively. CONCLUSIONS: The CTONG scoring system, as an objective evaluation model that involves multiple parameters, is a breakthrough method for evaluating the therapeutic value of lung cancer treatment options in China, which is worthy of further verification in future clinical practice.

Manifestation of severe pneumonia in anti-PL-7 antisynthetase syndrome and B cell lymphoma: A case report.

BACKGROUND: Antisynthetase syndrome (ASS) is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever, polymyositis-dermatomyositis and interstitial lung disease. It is, however, rare to observe ASS association with B cell lymphoma presenting severe pneumonia as the first clinical manifestation. CASE SUMMARY: We evaluated a 59-year-old male patient who presented with cough with sputum, shortness of breath and fever for 13 d. A chest computed tomography radiograph revealed bilateral diffuse ground-glass infiltrates in both upper fields, left lingual lobe and right middle lobe. Initially, the patient was diagnosed with severe community-acquired pneumonia and respiratory failure. He was empirically treated with broad-spectrum antibiotics, without improvement. Further analysis showed an ASS panel with anti-PL7 antibodies. Besides, electromyography evaluation demonstrated a manifestation of myogenic damage, while deltoid muscle biopsy showed irregular muscle fiber bundles especially abnormal lymphocyte infiltration. In addition, bone marrow biopsy revealed high invasive B cell lymphoma. Thus, the patient was diagnosed with a relatively rare anti-PL7 antibody positive ASS associated with B cell lymphoma. CONCLUSION: This case highlights that rapidly progressive lung lesions and acute hypoxemic respiratory failure associated with heliotrope rash and extremely high lactate dehydrogenase level should be considered as the characteristics of non-infectious diseases, especially ASS and B cell lymphoma.

Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study.

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways may delay therapeutic resistance in advanced non-small cell lung cancer (NSCLC). This phase 3 study investigated the efficacy and safety of an erlotinib plus bevacizumab regimen in untreated patients with advanced NSCLC. In total, 311 patients received bevacizumab plus erlotinib (n = 157) or erlotinib only (n = 154). Progression-free survival (PFS) was 17.9 months (95% confidence interval [CI], 15.2-19.9) for bevacizumab plus erlotinib and 11.2 months (95% CI, 9.7-13.8) for erlotinib only (hazard ratio [HR] = 0.55; 95% CI, 0.41-0.73; p < 0.001). A brain metastases subgroup treated with bevacizumab plus erlotinib also showed improved PFS (HR = 0.48; 95% CI, 0.27-0.84; p = 0.008). Grade ≥3 treatment-related adverse events occurred in 86 (54.8%) and 40 (26.1%) patients, respectively. Bevacizumab plus erlotinib significantly improved PFS in patients with untreated metastatic EGFR-mutated NSCLC, including those with brain metastases at baseline.

Sarcoidosis mimicking metastases in an echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase positive non-small-lung cancer patient: A case report.

BACKGROUND: Rearrangements of the anaplastic lymphoma kinase (ALK) gene (ALK-positive) represent an oncogenic driver in approximately 3%-5% of non-small-lung cancer (NSCLC) patients. Sarcoidosis is a multisystem disease, and its reported incidence in Asia is 1 or less per 100000 people per year. The co-occurrence of sarcoidosis and ALK-positive NSCLC is rare, and ALK-positive lung cancer is likely to spread quickly. Therefore, the co-occurrence of sarcoidosis is more easily misdiagnosed as metastatic lung cancer by radiological examination. CASE SUMMARY: A 50-year-old man had a nodule in the left superior lobe, many small nodules in left superior and right lungs, and enlarged bilateral hilar, mediastinal, and right supraclavicular lymph nodes. Computed tomography-guided pulmonary biopsy of the nodule in the left superior lobe revealed echinoderm microtubule-associated protein-like 4 gene-ALK positive NSCLC with concomitant noncaseating granuloma. This patient was treated with crizotinib. Thirty days later, a chest computed tomography scan revealed a dramatic decrease in the size of the left superior lobe nodule; however, the lesions in the right lung progressed. The right supraclavicular lymph nodes showed granulomas, and no tumor cells were identified in the specimens. The angiotensin-converting enzyme level was high. After 1 wk of methylprednisolone treatment, a significant response of all lesions was revealed. Following radical resection of the lung cancer, noncaseating granulomas were observed in both lung tissues and lymph nodes, which resulted in a diagnosis of echinoderm microtubule-associated protein-like 4-ALK positive NSCLC accompanied with sarcoidosis. CONCLUSION: Our experience illustrates that pathological evidence is needed to confirm metastatic disease, especially when some suspected metastatic lesions are negative for malignancy.

Fruquintinib with gefitinib as first-line therapy in patients carrying EGFR mutations with advanced non-small cell lung cancer: a single-arm, phase II study.

BACKGROUND: Fruquintinib is an oral vascular endothelial growth factor receptor inhibitor. Previous gefitinib studies with anti-angiogenics show promising efficacy. This phase II trial assessed efficacy and safety of fruquintinib in combination with gefitinib, in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Fifty patients with stage IIIB/IV NSCLC and an epidermal growth factor receptor (EGFR) exon-19 deletion or exon-21 L858R mutation were enrolled between January 2017 and June 2019. Per protocol (version 1.0), patients received 4 mg fruquintinib once daily (qd) Days 1-21 of Cycle 1, using a 3-week-on/1-week-off schedule, plus continuous gefitinib 250 mg qd. If tolerated, patients proceeded to fruquintinib 5 mg qd (fruquintinib 5 mg group, n=26). Following protocol updates, dose escalation of fruquintinib from 4 mg qd to 5 mg qd was not allowed. The primary efficacy endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), disease control rate (DCR), time to response, duration of response and adverse events (AEs). RESULTS: ORR was 73.5% (95% CI, 58.9-85.1) and DCR was 98.0% (95% CI, 89.2-100.0). Median PFS was 14.7 months for both groups; PFS was highest for patients with exon-19 deletion (16.5 months; 95% CI, 12.9-21.2). Grade ≥3 treatment-emergent AEs occurred in 17 (65.3%; fruquintinib 5 mg,) and 11 patients (45.8%; 4 mg). Serious AEs were recorded for nine patients (fruquintinib 5 mg, six patients; 4 mg, three). CONCLUSIONS: Fruquintinib and gefitinib treatment showed an acceptable safety profile and promising efficacy in patients with NSCLC.

Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer: 2-year follow-up from a randomized, open-label, phase 3 study (CheckMate 078).

BACKGROUND: In the phase 3 CheckMate 078 study, nivolumab showed significant overall survival (OS) benefit and superior tolerability versus docetaxel in a predominantly Chinese patient population with non-small cell lung cancer (NSCLC). However, data on long-term outcomes with immunotherapy in Asian patients are limited. We report 2-year efficacy and safety data. METHODS: Patients with advanced/metastatic NSCLC and disease progression after platinum-doublet chemotherapy were randomized 2:1 to nivolumab (3 mg/kg every 2 weeks; n = 338) or docetaxel (75 mg/m2 every 3 weeks; n = 166) until progression, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was OS; secondary endpoints included progression-free survival, objective response rate, and safety. RESULTS: After 25.9 months minimum follow-up, 21 patients (6 %) remained on nivolumab versus 0 on docetaxel. Median OS was 11.9 months with nivolumab versus 9.5 months with docetaxel (HR: 0.75; 95 % CI: 0.61-0.93); 2-year OS rates were 28 % versus 18 %, respectively. Survival benefits were observed across a variety of predefined subgroups. At 2 years, 39 % and 0 % of responders had ongoing responses with nivolumab and docetaxel, respectively. Grade 3-4 treatment-related adverse events occurred in 12 % of patients with nivolumab versus 47 % with docetaxel, leading to discontinuation in 4 % and 5 % of patients, respectively. No new treatment-related deaths occurred. CONCLUSION: At 2 years, nivolumab maintained a favorable safety profile and continued to demonstrate superior OS versus docetaxel in this predominantly Chinese patient population with previously treated NSCLC. These data are consistent with long-term outcomes from the global CheckMate 017/057 studies.

Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

Clinical Characteristics and Outcomes of Acute Lung Injury Caused by Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Retrospective Cohort Study from a Single Institution in China.

BACKGROUND: Acute lung injury (ALI) is a rare but life-threatening pulmonary complication of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). The aim of this study was to characterize the common risk factors, clinical features, imaging findings, treatments, and outcomes of acute lung injury caused by TACE. METHODS: A retrospective study was performed on all TACE-associated ALI cases that were diagnosed at authors' hospital from January 2015 to June 2018. RESULTS: The study included 14 ALI cases where the mean age of patients was 60.9 ± 11.7 years (range 41-82 years), with a mean onset time of 2.4 ± 1.6 d after TACE. Of the 14 patients, 8 patients (57.1%) developed acute respiratory distress syndrome (ARDS). 7 patients (50%) had underlying chronic respiratory disease and hepatic arteriovenous fistula was detected in 6 patients (42.6%), both of which were significantly higher than control group (P < 0.05). Dyspnea (92.9%) was the most common symptoms. Pleural effusion (64.3%), diffuse pulmonary infiltration (42.9%), and accumulation of Lipiodol in lung field (42.9%) were frequent radiologic abnormalities. 11 patients (78.6%) achieved remission after treatment, and the 30-day mortality rate was approximately 21.4%. Patient's median survival time after the development of ALI was merely 4.3 months, which was obviously worse than control group (4.3 months vs. 13.5 months, P < 0.05). CONCLUSION: This study illustrates that TACE-associated ALI is a rare pulmonary complication with a high mortality rate. We infer that pulmonary Lipiodol embolization might be one of the main causes of TACE-associated ALI. Thus, HCC patients who are at high risk should be closely evaluated and monitored during TACE to avoid such potentially fatal complication.

Female genital tract metastasis of lung adenocarcinoma with EGFR mutations: Report of two cases.

BACKGROUND: The female genital tract is an uncommon site of involvement for extra-genital malignancies. Ovarian metastases have been described as disseminations of lung adenocarcinoma; rare cases of secondary localizations in the cervix, adnexa, and vagina have also been reported in the literature. Here, we report two cases of advanced lung adenocarcinoma with female genital tract metastasis. CASE SUMMARY: The first case was a 41-year-old woman with stage IV lung adenocarcinoma metastasizing to the cervix. Immunohistochemistry of the cervical biopsy specimen revealed thyroid transcription factor (TTF)-1(+), cytokeratin (CK)-7(+), and (CK)-20(-). Gene mutational analysis showed epidermal growth factor receptor (EGFR) L858R mutation in exon 21. She had a positive response to gefitinib, for both the pulmonary mass and cervical neoplasm. The second case was a 29-year-old woman who was diagnosed with stage IV lung adenocarcinoma with EGFR mutation. After 12 mo of treatment with icotinib, ovarian biopsy showed adenocarcinoma with CDX2(-), TTF-1(+++), PAX8(-), CK-7(+++), CK-20(++), and Ki67(15%+), accompanied with EGFR 19-del mutation and T790M mutation. CONCLUSION: Immunohistochemistry and gene mutational testing have greatly helped in locating the initial tumor site when both pulmonary and female genital tract neoplasms exist.

Analysis of the Genotypes in a Chinese Population with Increased Hb A2 and Low Hematological Indices.

Increased Hb A2 is considered the most reliable hematological finding for the identification of ß-thalassemia (ß-thal) carriers. The aim of this study was to determine the underlying genetic factors associated with a high Hb A2 level in a Chinese population. Subjects were recruited from couples preparing for pregnancy who participated in the thalassemia screening program during a 2-year period. DNA analyses were used for diagnosis of ß-thal and other genetic factors. A total of 5985 adults who screened positive for ß-thal were recruited. Of these, 5933 (99.1%) were detected to have a ß-thal mutation. In the remaining 52 (0.9%) individuals without mutations involving the ß-globin gene cluster, 16 were found to have Krüppel-like factor 1 (KLF1) gene variants, and two had an α-globin gene triplication. There were still 34 individuals with unknown genetic factors for their raised Hb A2 values. The results of this study indicate that genetic factors other than ß-thal can rarely contribute to the elevation of Hb A2. These subjects usually have borderline microcytic red cell indices and Hb A2 values.